| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Journal of Clinical Endocrinology & Metabolism, Vol 78, 1360-1367, Copyright © 1994 by Endocrine Society
ARTICLES |
AJ Morales, JJ Nolan, JC Nelson and SS Yen
Department of Reproductive Medicine, University of California School of Medicine, La Jolla 92093-0802.
Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20- min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.
This article has been cited by other articles:
 |
|
 |
|
  E. M. Gurnell, P. J. Hunt, S. E. Curran, C. L. Conway, E. M. Pullenayegum, F. A. Huppert, J. E. Compston, J. Herbert, and V. K. K. Chatterjee Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 400 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Hartkamp, R Geenen, G L R Godaert, H Bootsma, A A Kruize, J W J Bijlsma, and R H W M Derksen Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome: a randomised controlled trial Ann Rheum Dis, January 1, 2008; 67(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, H. Si, K. A. Reynolds, W. Zhen, Z. Jia, and J. S. Dillon Dehydroepiandrosterone Protects Vascular Endothelial Cells against Apoptosis through a G{alpha}i Protein-Dependent Activation of Phosphatidylinositol 3-Kinase/Akt and Regulation of Antiapoptotic Bcl-2 Expression Endocrinology, July 1, 2007; 148(7): 3068 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Panjari and S. R. Davis DHEA therapy for women: effect on sexual function and wellbeing Hum. Reprod. Update, May 1, 2007; 13(3): 239 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Nair, R. A. Rizza, P. O'Brien, K. Dhatariya, K. R. Short, A. Nehra, J. L. Vittone, G. G. Klee, A. Basu, R. Basu, et al. DHEA in Elderly Women and DHEA or Testosterone in Elderly Men N. Engl. J. Med., October 19, 2006; 355(16): 1647 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Muller, A. W. van den Beld, Y. T. van der Schouw, D. E. Grobbee, and S. W. J. Lamberts Effects of Dehydroepiandrosterone and Atamestane Supplementation on Frailty in Elderly Men J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3988 - 3991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Brooke, L. A. Kalingag, F. Miraki-Moud, C. Camacho-Hubner, K. T. Maher, D. M. Walker, J. P. Hinson, and J. P. Monson Dehydroepiandrosterone Improves Psychological Well-Being in Male and Female Hypopituitary Patients on Maintenance Growth Hormone Replacement J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3773 - 3779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Jankowski, W. S. Gozansky, R. S. Schwartz, D. J. Dahl, J. M. Kittelson, S. M. Scott, R. E. Van Pelt, and W. M. Kohrt Effects of Dehydroepiandrosterone Replacement Therapy on Bone Mineral Density in Older Adults: A Randomized, Controlled Trial J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2986 - 2993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Labrie Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA. Endocr. Relat. Cancer, June 1, 2006; 13(2): 335 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Arlt Androgen therapy in women Eur. J. Endocrinol., January 1, 2006; 154(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iruthayanathan, Y.-H. Zhou, and G. V. Childs Dehydroepiandrosterone Restoration of Growth Hormone Gene Expression in Aging Female Rats, in Vivo and in Vitro: Evidence for Actions via Estrogen Receptors Endocrinology, December 1, 2005; 146(12): 5176 - 5187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Labrie, V Luu-The, A Belanger, S-X Lin, J Simard, G Pelletier, and C Labrie Is dehydroepiandrosterone a hormone? J. Endocrinol., November 1, 2005; 187(2): 169 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kaufman and A. Vermeulen The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications Endocr. Rev., October 1, 2005; 26(6): 833 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Bancroft The endocrinology of sexual arousal J. Endocrinol., September 1, 2005; 186(3): 411 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Chang, Y.-C. Ou, S.-L. Raung, and C.-J. Chen Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection J. Gen. Virol., September 1, 2005; 86(9): 2513 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. van Thiel, J. A. Romijn, A. M. Pereira, N. R. Biermasz, F. Roelfsema, A. van Hemert, B. Ballieux, and J. W. A. Smit Effects of Dehydroepiandrostenedione, Superimposed on Growth Hormone Substitution, on Quality of Life and Insulin-Like Growth Factor I in Patients with Secondary Adrenal Insufficiency: A Randomized, Placebo-Controlled, Cross-Over Trial J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3295 - 3303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Boone and K. M. Shields Dietary supplements for female sexual dysfunction Am. J. Health Syst. Pharm., March 15, 2005; 62(6): 574 - 580. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dhatariya, M. L. Bigelow, and K. S. Nair Effect of Dehydroepiandrosterone Replacement on Insulin Sensitivity and Lipids in Hypoadrenal Women Diabetes, March 1, 2005; 54(3): 765 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Schmidt, R. C. Daly, M. Bloch, M. J. Smith, M. A. Danaceau, L. Simpson St. Clair, J. H. Murphy, N. Haq, and D. R. Rubinow Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression Arch Gen Psychiatry, February 1, 2005; 62(2): 154 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Villareal and J. O. Holloszy Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men: A Randomized Controlled Trial JAMA, November 10, 2004; 292(18): 2243 - 2248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vanderschueren, L. Vandenput, S. Boonen, M. K. Lindberg, R. Bouillon, and C. Ohlsson Androgens and Bone Endocr. Rev., June 1, 2004; 25(3): 389 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Soma, N. A. Alday, M. Hau, and B. A. Schlinger Dehydroepiandrosterone Metabolism by 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase in Adult Zebra Finch Brain: Sex Difference and Rapid Effect of Stress Endocrinology, April 1, 2004; 145(4): 1668 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Zhou, K. Tanaka, M. J. Soares, and G. You Characterization of an organic anion transport system in a placental cell line Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1103 - E1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Leblanc, C. Labrie, A. Belanger, B. Candas, and F. Labrie Bioavailability and Pharmacokinetics of Dehydroepiandrosterone in the Cynomolgus Monkey J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4293 - 4302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S T. Valtysdottir, L Wide, and R Hallgren Mental wellbeing and quality of sexual life in women with primary Sjogren's syndrome are related to circulating dehydroepiandrosterone sulphate Ann Rheum Dis, September 1, 2003; 62(9): 875 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kawano, H. Yasue, A. Kitagawa, N. Hirai, T. Yoshida, H. Soejima, S. Miyamoto, M. Nakano, and H. Ogawa Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3190 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Morley and H. M. Perry III Androgens and Women at the Menopause and Beyond J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M409 - 416. [Full Text] [PDF]
|
|
|
|
|
|
F. Labrie, V. Luu-The, C. Labrie, A. Belanger, J. Simard, S.-X. Lin, and G. Pelletier Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone Endocr. Rev., April 1, 2003; 24(2): 152 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. W. Wu and A. von Eckardstein Androgens and Coronary Artery Disease Endocr. Rev., April 1, 2003; 24(2): 183 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Percheron, J.-Y. Hogrel, S. Denot-Ledunois, G. Fayet, F. Forette, E.-E. Baulieu, M. Fardeau, and J.-F. Marini Effect of 1-Year Oral Administration of Dehydroepiandrosterone to 60- to 80-Year-Old Individuals on Muscle Function and Cross-sectional Area: A Double-blind Placebo-Controlled Trial Arch Intern Med, March 24, 2003; 163(6): 720 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Blazer Depression in Late Life: Review and Commentary J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2003; 58(3): M249 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Strous, R. Maayan, R. Lapidus, R. Stryjer, M. Lustig, M. Kotler, and A. Weizman Dehydroepiandrosterone Augmentation in the Management of Negative, Depressive, and Anxiety Symptoms in Schizophrenia Arch Gen Psychiatry, February 1, 2003; 60(2): 133 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Z. Leder, K. M. LeBlanc, C. Longcope, H. Lee, D. H. Catlin, and J. S. Finkelstein Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5449 - 5454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Gordon, E. Grace, S. J. Emans, H. A. Feldman, E. Goodman, K. A. Becker, C. J. Rosen, C. M. Gundberg, and M. S. LeBoff Effects of Oral Dehydroepiandrosterone on Bone Density in Young Women with Anorexia Nervosa: A Randomized Trial J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4935 - 4941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Lasley, N. Santoro, J. F. Randolf, E. B. Gold, S. Crawford, G. Weiss, D. S. McConnell, and M. F. Sowers The Relationship of Circulating Dehydroepiandrosterone, Testosterone, and Estradiol to Stages of the Menopausal Transition and Ethnicity J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3760 - 3767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Johannsson, P. Burman, L. Wiren, B. E. Engstrom, A. G. Nilsson, M. Ottosson, B. Jonsson, B.-A. Bengtsson, and F. A. Karlsson Low Dose Dehydroepiandrosterone Affects Behavior in Hypopituitary Androgen-Deficient Women: A Placebo-Controlled Trial J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2046 - 2052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kunelius, O. Lukkarinen, M. L. Hannuksela, O. Itkonen, and J. S. Tapanainen The Effects of Transdermal Dihydrotestosterone in the Aging Male: A Prospective, Randomized, Double Blind Study J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1467 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]
|
|
|
|
 |
|
 C. Du, Q. Guan, M. W. Khalil, and S. Sriram Stimulation of Th2 Response by High Doses of Dehydroepiandrosterone in KLH-Primed Splenocytes Experimental Biology and Medicine, December 1, 2001; 226(11): 1051 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Arlt, F. Callies, I. Koehler, J. C. van Vlijmen, M. Fassnacht, C. J. Strasburger, M. J. Seibel, D. Huebler, M. Ernst, M. Oettel, et al. Dehydroepiandrosterone Supplementation in Healthy Men with an Age-Related Decline of Dehydroepiandrosterone Secretion J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4686 - 4692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Crone, G. Gabriel, and T. N. Wise Non-Herbal Nutritional Supplements--The Next Wave: A Comprehensive Review of Risks and Benefits for the C-L Psychiatrist Psychosomatics, August 1, 2001; 42(4): 285 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. C. Yen Dehydroepiandrosterone sulfate and longevity: New clues for an old friend PNAS, July 17, 2001; 98(15): 8167 - 8169. [Full Text] [PDF]
|
|
|
|
|
|
L. Mazat, S. Lafont, C. Berr, B. Debuire, J.-F. Tessier, J.-F. Dartigues, and E.-E. Baulieu Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: Relationship to gender, subjective health, smoking habits, and 10-year mortality PNAS, June 20, 2001; (2001) 121177998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Callies, M. Fassnacht, J. C. van Vlijmen, I. Koehler, D. Huebler, M. J. Seibel, W. Arlt, and B. Allolio Dehydroepiandrosterone Replacement in Women with Adrenal Insufficiency: Effects on Body Composition, Serum Leptin, Bone Turnover, and Exercise Capacity J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1968 - 1972. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. A. Feldman, C. B. Johannes, A. B. Araujo, B. A. Mohr, C. Longcope, and J. B. McKinlay Low Dehydroepiandrosterone and Ischemic Heart Disease in Middle-aged Men: Prospective Results from the Massachusetts Male Aging Study Am. J. Epidemiol., January 1, 2001; 153(1): 79 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Monteleone, M. Luisi, B. Colurcio, E. Casarosa, P. Monteleone, R. Ioime, A. R. Genazzani, and M. Maj Plasma Levels of Neuroactive Steroids Are Increased in Untreated Women With Anorexia Nervosa or Bulimia Nervosa Psychosom Med, January 1, 2001; 63(1): 62 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kalmijn, J. A. M. J. L. Janssen, H. A. P. Pols, S. W. J. Lamberts, and M. M. B. Breteler A Prospective Study on Circulating Insulin-Like Growth Factor I (IGF-I), IGF-Binding Proteins, and Cognitive Function in the Elderly J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4551 - 4555. [Abstract] [Full Text]
|
|
|
|
|
|
P. J. Hunt, E. M. Gurnell, F. A. Huppert, C. Richards, A. T. Prevost, J. A. H. Wass, J. Herbert, and V. K. K. Chatterjee Improvement in Mood and Fatigue after Dehydroepiandrosterone Replacement in Addison's Disease in a Randomized, Double Blind Trial J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4650 - 4656. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Khalil, J.-P. Fortin, J.-G. LeHoux, and T. Fülöp Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation J. Lipid Res., October 1, 2000; 41(10): 1552 - 1561. [Abstract] [Full Text]
|
|
|
|
 |
|
 P.R. Casson, M.S. Lindsay, M.D. Pisarska, S.A. Carson, and J.E. Buster Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series Hum. Reprod., October 1, 2000; 15(10): 2129 - 2132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Legrain, C. Massien, N. Lahlou, M. Roger, B. Debuire, B. Diquet, G. Chatellier, M. Azizi, V. Faucounau, H. Porchet, et al. Dehydroepiandrosterone Replacement Administration: Pharmacokinetic and Pharmacodynamic Studies in Healthy Elderly Subjects J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3208 - 3217. [Abstract] [Full Text]
|
|
|
|
|
|
E.-E. Baulieu, G. Thomas, S. Legrain, N. Lahlou, M. Roger, B. Debuire, V. Faucounau, L. Girard, M.-P. Hervy, F. Latour, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: Contribution of the DHEAge Study to a sociobiomedical issue PNAS, April 11, 2000; 97(8): 4279 - 4284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Brown, M. D. Vukovich, R. L. Sharp, T. A. Reifenrath, K. A. Parsons, and D. S. King Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men J Appl Physiol, December 1, 1999; 87(6): 2274 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Barnhart, E. Freeman, J. A. Grisso, D. J. Rader, M. Sammel, S. Kapoor, and J. E. Nestler The Effect of Deydroepiandrosterone Supplementation to Symptomatic Perimenopausal Women on Serum Endocrine Profiles, Lipid Parameters, and Health-Related Quality of Life J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3896 - 3902. [Abstract] [Full Text]
|
|
|
|
|
|
T. Remer and F. Manz Role of Nutritional Status in the Regulation of Adrenarche J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3936 - 3944. [Abstract] [Full Text]
|
|
|
|
|
|
A. J. Lerner Alzheimer's Disease in Males: Endocrine Issues and Prospects J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3416 - 3419. [Full Text] [PDF]
|
|
|
|
|
|
W. Arlt, F. Callies, J. C. van Vlijmen, I. Koehler, M. Reincke, M. Bidlingmaier, D. Huebler, M. Oettel, M. Ernst, H. M. Schulte, et al. Dehydroepiandrosterone Replacement in Women with Adrenal Insufficiency N. Engl. J. Med., September 30, 1999; 341(14): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Oelkers Dehydroepiandrosterone for Adrenal Insufficiency N. Engl. J. Med., September 30, 1999; 341(14): 1073 - 1074. [Full Text]
|
|
|
|
|
|
C. N. Epperson, K. L. Wisner, and B. Yamamoto Gonadal Steroids in the Treatment of Mood Disorders Psychosom Med, September 1, 1999; 61(5): 676 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Rosen Serum Insulin-like Growth Factors and Insulin-like Growth Factor-binding Proteins: Clinical Implications Clin. Chem., August 1, 1999; 45(8): 1384 - 1390. [Abstract] [Full Text] [PDF]
|
|
